Stevanin G, Dürr A, David G, Didierjean O, Cancel G, Rivaud S, Tourbah A, Warter J M, Agid Y, Brice A
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Neurology. 1997 Nov;49(5):1243-6. doi: 10.1212/wnl.49.5.1243.
The mutation involved in spinocerebellar ataxia type 6 (SCA6) is a small CAG expansion in the alpha-1A subunit of the voltage-dependent calcium channel gene. We looked for this mutation in 91 families with autosomal-dominant cerebellar ataxias and found that SCA6 is a minor locus in our series (2%) and is rare in France (1%). Furthermore, we did not detect the SCA6 mutation on 146 sporadic cases with isolated cerebellar ataxia or olivopontocerebellar atrophy. The normal and expanded alleles ranged from 4 to 15 and 22 to 28 CAG repeats, respectively, and age at onset was correlated to CAG repeat length (r = -0.87). In contrast with other SCA, the expanded allele was stable during transmission. Clinically, SCA6 patients (n = 12) presented with moderate to severe cerebellar ataxia with a lower frequency of associated signs compared with other SCA and a mean age at onset of 45 +/- 14 years (range, 24 to 67). MRI showed extensive cerebellar atrophy but not of the brainstem or cerebral cortex.
6型脊髓小脑共济失调（SCA6）所涉及的突变是电压依赖性钙通道基因α-1A亚基中的一个小的CAG重复序列扩增。我们在91个常染色体显性遗传性小脑共济失调家系中寻找此突变，发现SCA6在我们的研究系列中是一个次要位点（2%），在法国较为罕见（1%）。此外，我们在146例孤立性小脑共济失调或橄榄桥脑小脑萎缩的散发病例中未检测到SCA6突变。正常和扩增的等位基因分别具有4至15个和22至28个CAG重复序列，发病年龄与CAG重复序列长度相关（r = -0.87）。与其他脊髓小脑共济失调不同，扩增的等位基因在传递过程中是稳定的。临床上，12例SCA6患者表现为中度至重度小脑共济失调，与其他脊髓小脑共济失调相比，相关体征出现频率较低，平均发病年龄为45±14岁（范围为24至67岁）。MRI显示广泛的小脑萎缩，但脑干或大脑皮质未出现萎缩。
